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Preclinical data indicated that seroquel (ICI 204 636), a dibenzothiazepine with 5-HT2 and D2-like receptor antagonistic properties, might be an effective antipsychotic agent, causing fewer extrapyramidal side effects than typical neuroleptics. In the present study, 12 patients suffering from schizophrenia or schizophreniform disorder with predominantly positive symptomatology were treated in an open clinical trial for 4 weeks with seroquel at a maximum dosage of 750 mg/day. The drug was generally well tolerated, and virtually no adverse extrapyramidal side effects such as acute dystonia, parkinsonism or akathisia were observed. Total scores for BPRS (item score 0-6; baseline: 42.0 +/- 2.3; mean +/- SEM), SAPS (64.5 +/- 4.8) and SANS (55.0 +/- 4.3) showed a moderate decrease at the end of treatment (BPRS: 30.0 +/- 3.5; SAPS: 36.1 +/- 6.7; SANS: 42.5 +/- 5.9), when intention-to-treat analysis was applied. There were considerable interindividual differences in treatment response, with some subjects showing almost full remission of positive symptoms, in contrast to about half of the patients who showed no satisfactory clinical improvement. Interestingly, patients showing good antipsychotic response reported slight initial side effects like mild sedation. Prolactin and TSH levels were not altered during seroquel administration. As to pharmaco-EEG investigations, seroquel caused a moderate increase of the absolute power in the alpha, theta, and beta frequency bands, paralleled by a decrease of delta activity. There were no signs of paroxysmal EEG activity under seroquel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Seroquel (ICI 204 636), a putative "atypical" antipsychotic, in schizophrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinological and EEG parameters. 765 71

We have previously shown that reproductive seasonality of bucks was prevented for 2 consecutive years by short photoperiodic cycles. To determine the effect of the length of treatment time on bucks subjected to the same photoperiod conditions, experiments were continued for a third consecutive year on 3 groups of 6 Alpine and Saanen bucks. The control group was kept under natural photoperiodic conditions, while the experimental groups were exposed alternately to 1 month of long days and 1 month of short days (group 2M) or to 2 months of long days and 2 months of short days (group, 4M). Prolactin profiles indicated that bucks from both experimental groups responded adequately to rapid photoperiod changes as their plasma prolactin levels were significantly higher in long days (mean +/- SEM; 2M: 61.1 +/- 15.9 ng/ml; 4M: 102.2 +/- 13.5 ng/ml) than in short days (2M: 35.3 +/- 8.2 ng/ml; 4M: 46.1 +/- 9.0 ng/ml). Testosterone secretion was also dependent on day length (P < 0.0001), since testosterone concentrations of experimental animals were higher during long days (2M: 7.0 +/- 0.7 ng/ml; 4M: 10.2 +/- 1.1 ng/ml) than during short days (2M: 4.3 +/- 0.4 ng/ml; 4M: 5.0 +/- 0.9 ng/ml). Furthermore, controls displayed a high level of sexual behavior (always higher than 10%) and the proportion of bucks unable to ejaculate was significantly lower (P < 0.01) than the experimental animals (2M: 25.6%; 4M: 28.1%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maintenance of sperm production in bucks during a third year of short photoperiodic cycles. 814 42

The sequence of structural changes in goat hair follicles was investigated using melatonin implants to advance and synchronize spring hair growth. Ten pasture fed cashmere wethers each received a controlled release formulation of 70 mg of melatonin on September 1 1989, and showed plasma melatonin elevated above physiological levels over 14 days post-treatment (914 +/- 154 pg/ml [mean +/- SEM] on day 14). In ten untreated animals, daytime plasma melatonin was 19.9 +/- 4.7 pg/ml. Histological examination of skin biopsies taken over the 14 days from the start of the experiment showed that primary hair follicles of goats with manipulated hormone levels had initiated fiber growth (entered proanagen), whereas primary follicles of untreated goats largely remained in the quiescent phase (telogen). A standardized terminology was used to describe the sequence of events during induced proanagen. Structural reorganization of follicles began in treated animals between days 6 and 12 post-treatment, and emergent fibers grew by day 24. Advancement of spring fiber growth was associated with a suppression of the normal rise in plasma prolactin concentration. Prolactin levels in untreated goats increased from 7.4 +/- 1.8 ng/ml on day 1 to 12.8 +/- 1.6 ng/ml on day 14, but declined in treated goats from 6.3 +/- 2.3 ng/ml to 2.2 +/- 0.8 ng/ml over the same period.
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PMID:Fiber growth initiation in hair follicles of goats treated with melatonin. 837 51

Blood samples, morphometric measurements and behavioural data were collected weekly for 52 weeks from six adult Eld's deer stags exposed to natural fluctuations in photoperiod (38 degrees N latitude). Mean (+/- SEM) serum LH concentrations reached peak values in the autumn (October), three months before FSH and testosterone concentrations reached peak values in early winter (January). Prolactin concentrations were inversely related (r = -0.733, P < 0.001) to LH and directly related to daylength, and maximal concentrations were observed during mid-summer (July) and minimal concentrations during early winter (January). The temporal pattern of circulating inhibin was positively correlated with FSH (r = 0.88, P < 0.001), but lagged behind the seasonal FSH increase by 1-3 weeks. Antler length, body weight and chest girth were maximal during pre-rut (December-January). Maximal scrotal circumference and combined testes volume were observed in mid-winter (February), whereas peak neck girth and behavioural aggression occurred 1-3 months later (March-May). On the basis of quarterly electroejaculation results, motile spermatozoa were produced in all seasons. However, the greatest number of motile spermatozoa per ejaculate was observed during the winter and spring, whereas the highest incidence of sperm pleiomorphisms (> 80%) was detected in the autumn. Histological assessments of the regressed testis (July) revealed fewer germ cells undergoing spermatogenesis and an increased incidence of degenerating and abnormal cell types. In summary, Eld's deer exhibit a circannual hypothalamic-pituitary-gonadal cycle with onset of pituitary activation occurring during the autumn and winter, whereas gonadal activity peaks during the winter and spring as daylengths are increasing. Marked circannual variations in circulating prolactin suggest that Eld's deer may use photoperiodic cues to modulate seasonal fertility; however, the existence of an endogenous seasonal rhythm operating independently of photoperiod cannot be excluded.
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PMID:Circannual inter-relationships among reproductive hormones, gross morphometry, behaviour, ejaculate characteristics and testicular histology in Eld's deer stags (Cervus eldi thamin). 841 Aug 13

Prolactin (PRL) is a pituitary hormone that plays important roles in mammalian reproductive physiology, specially lactation. The regulation of PRL secretion shows important species differences. To study PRL regulation in a subhuman primate, the Cebus apella, we developed an heterologous radioimmunoassay using an antibody against rhesus PRL (anti-m5PRL) and a Cebus apella pituitary extract as PRL standard. The assay has a sensitivity that allows measurements of cebus PRL in small amounts of Cebus apella plasma obtained from animals in different physiological conditions. Plasma cebus PRL concentrations (+/-SEM) varied in different reproductive stages. PRL concentration in adult Cebus apella females that have regular menstrual cycles (161.6 +/- 15.0 mIU/ml) was similar to that found in adult (100.3 +/- 7.6 mIU/ml) and prepuberal males (101.2 +/- 3.9 mIU/ml). PRL concentration was higher in pregnant (677.8 +/- 11.8 mIU/ml) and in nursing (625.0 +/- 47.0 mIU/ml) Cebus apella females than in 15-d post-partum non-nursing (369.0 +/- 19.0 mIU/ml) and cycling females. PRL concentration in Cebus apella newborns (719.0 +/- 49.2 mIU/ ml) was similar to that found in pregnant and nursing females, and higher than in the other females as well as adult and prepuberal males. These differences in PRL concentration in different physiological conditions are similar to that observed in humans and other primates. A PRL response to thyrotropin releasing hormone (TRH) was demonstrated in 2 nursing Cebus apella females, similar to the response found in nursing woman and rhesus. Altogether, the data presented support the proposal that the assay developed to measure PRL in Cebus apella is an adequate tool to study the physiology of PRL in this species.
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PMID:Development of a radioimmunoassay for Cebus apella prolactin. 928 20

Beagle bitches were administered the dopamine D2 receptor agonist cabergoline in 3 groups of 5 animals each, starting on known days of the estrous cycle. Cabergoline treatment was started in either early anestrus (Days 93 to 108), mid-anestrus (Days 123 to 156), or late anestrus (Days 161 to 192) at doses of 5 ug/kg/d, per os, and was continued until the confirmation of induced proestrus or for 40 d. Reproductive parameters were compared with those in 5 control anestrous bitches (Days 90 to 150). In control bitches, the mean (+/- SEM) interval to the next proestrus (73+/-11 d) resulted in an interestrus interval (192+/-9 d) similar to that of the previous cycles (196+/-11 d). In 14 of the 15 cabergoline-treated bitches, the next proestrus occurred within 4 to 30 d, was premature in early and mid-anestrous bitches and developed with low variability within groups. The resulting intervals to proestrus in bitches treated with cabergoline in early anestrus (20+/-2 d), mid-anestrus (14+/-3 d) and late anestrus (6+/-1 d) resulted in interestrus intervals in those groups of 131+/-5, 166+/-7 and 196+/-2 d, respectively. In response to treatment, interestrus intervals were reduced (P<0.05) and more synchronous (P<0.05) in early and mid-anestrus bitches, and were more synchronous (P<0.05) in late-anestrous bitches compared with those of control bitches or those of the previous cycle. Periovulatory estradiol and progesterone profiles of induced cycles in treated bitches were similar to those of spontaneous cycles in control bitches. Four of 5 control bitches and 12 of the 14 responding cabergoline-treated bitches became pregnant and produced normal litters. Plasma prolactin concentrations at Days 2 and 5 of treatment (0.3+/-0.1 ng/mL) and at the onset of proestrus shortly before the end of treatment (0.4+/-0.1 ng/mL) were lower (P<0.05) than those present in anestrus prior to treatment (1.7+/-0.6 ng/mL) or in control bitches. Prolactin was also low at the onset of proestrus in control bitches (0.5+/-0.2 ng/mL). The results demonstrate that prolactin-lowering doses of the dopamine agonist cabergoline can terminate the normal obligate anestrus in dogs, and that the effect occurs more slowly in early anestrus than in mid or late anestrus.
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PMID:Effect of stage of anestrus on the induction of estrus by the dopamine agonist cabergoline in dogs. 1072 45

This study was carried out to investigate mammary tumorigenesis in growth hormone (GH) deficient spontaneous dwarf rats (SDR). At 50-60 days of age, the rats were divided into five groups. Group 1 received bovine (b) GH (prolonged release formulation) administered at a dose of 40-50 mg/kg body wt. in 50 microl weekly injections; group 2 received recombinant human insulin-like growth factor-I (IGF-I) at a dose of 1 mg/kg body wt./day administered via osmotic pumps; animals in group 3 were fitted with subcutaneous silastic capsule containing 30 microg 17 beta-estradiol (E2) plus 30 mg progesterone (P4), replaced every 2 months; group 4 received both bGH and E2 plus P4 treatments at the same doses as above, and control animals (group 5) received sham treatments (vegetable oil injection, silastic capsules containing cellulose). After 1 week of treatment, all animals were injected intraperitoneally with the carcinogen N-methyl-N-nitrosourea (MNU) at a dose of 50 mg/kg body wt. Other groups of animals, receiving identical hormonal treatment to those exposed to MNU, were treated for 10 days only and then sacrificed for assessment of circulating concentrations of hormones and mammary gland characteristics at the time of carcinogen exposure. The hormonal treatments of the animals exposed to the MNU were continued for an additional 20 weeks and mammary tumor development monitored by weekly palpation and tumors collected as necessary. The rats were weighed weekly. At the end of the treatment period, all animals were sacrificed and remaining tumors were collected. Rats in all groups continued to gain weight throughout the experimental period, but the largest weight gain was see in animals receiving GH either alone or with E2 and P4. Animals treated with IGF-I also gained weight compared to controls, but this weight gain was less than that seen in GH-treated rats. GH treatment alone increased mammary tumor incidence from 4.8% in controls to 100%. Average tumor load and latency in the GH-treated rats were 7.0 +/- 0.8 tumors/tumor-bearing rat (mean +/- SEM) and 57.3 +/- 2.7 days (mean +/- SEM), respectively. As in intact Sprague-Dawley rats, approximately 90% of the tumors that developed in the GH-treated rats were ovarian dependent for growth. IGF-I treatment also increased mammary tumor development to 62.5%. Average tumor load and latency in the IGF-I-treated rats were 1.6 +/- 0.4 tumors/tumor-bearing rat (mean +/- SEM) and 96.2 +/- 14.5 days (mean +/- SEM), respectively. However E2 + P4 treatments did not significantly alter tumorigenesis and, surprisingly, simultaneous treatment with E2 + P4 and GH obliterated the GH-stimulated increase in tumor development. Prolactin (PRL) did not appear to influence mammary tumorigenesis in the SDRs, as untreated SDRs had significantly elevated serum concentration of PRL as compared with normal Sprague-Dawley (SD) rats, whereas GH-treated SDRs had PRL levels similar to that of normal SD rats. No obvious structural characteristics were associated with high or low susceptibility to mammary tumorigenesis, as assessed by mammary gland whole mounts from the different animal groups sacrificed at the time of carcinogen administration. Enhanced expression of the extracellular signal-regulated kinase 1/2 (ERK1/2), and activation (phosphorylation) of ERK1/2 were associated with an increase in mammary tumorigenesis. Similarly, the expression of the estrogen receptor-alpha (ER alpha) was significantly elevated in animal groups with the highest susceptibility to tumorigenesis, whereas the levels of cyclin D1 expression were not related to mammary tumorigenesis.
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PMID:Mammary tumorigenesis in growth hormone deficient spontaneous dwarf rats; effects of hormonal treatments. 1552 71

Eight nulliparous Angus and Angus crossbred heifers, which had been ovariectomized and treated with estradiol-17beta (E(2)) S.Q. implants for 6 months, were used to determine the effects of exogenous melatonin on serum gonadotropin and prolactin concentrations. Melatonin (15 mg) or corn oil (vehicle) was administered as a single i.m. injection at 1600 h daily for 12 weeks (March 19 to June 4, 1982). Blood samples taken weekly via jugular venipuncture at approximately 1100 h were assayed for luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin and E(2). At 4-week intervals, animals were fitted with indwelling jugular cannulae at 1100 h and samples were taken for 4 h at 15-min intervals. These samples were used to estimate pulsatile patterns of LH, FSH and prolactin. On the day of the first 15-min sampling, additional blood samples were collected at 30 min intervals from 1500 to 2200 h to determine the acute effect of melatonin injection on concentrations of LH, FSH and prolactin. Melatonin did not affect concentrations of FSH collected at weekly intervals (P=0.03) but tended to inhibit the decrease in concentrations of LH seen in the heifers treated with vehicle (P=0.12). There was a melatonin x time interaction for FSH (P=0.04) and a tendency for this interaction for LH (P=0.11). Circulating concentrations of prolactin were not different between treatment groups (P=0.83) nor was there a melatonin x time interaction (P=0.03). Estradiol was higher in the melatonin treated group (P=0.03) (15.58 +/- 4.17 versus 8.25 +/- 1.25 pg/ml) (X +/- SEM) and the melatonin x time interaction was significant (P=0.001). There was a tendency for a melatonin x time interaction for FSH pulse frequency (P=0.10). Prolactin pulse duration tended to decrease in response to melatonin treatment (P=0.14) (15.92 +/- 9.29 versus 11.04 +/- 4.57 min). These data do not support the hypothesis that melatonin decreases prolactin concentrations in cattle and indicates that other factors must mediate photoperiod regulation of this hormone. However, the interpretation of these data is less clear concerning the hypothesis that melatonin may maintain elevated concentrations of gonadotropins in the presence of increasing photoperiod. Concentrations of FSH appeared to be more affected by melatonin than LH; consistent with previous observations that FSH may be more affected than LH by changes in photoperiod (2). But neither LH or FSH concentrations were clearly shown to be consistantly elevated in the melatonin treatment group.
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PMID:The effect of exogenous melatonin administration on gonadotropin and prolactin patterns in ovariectomized estradiol-treated heifers exposed to increasing photoperiod. 1672 9

Hypothyroidism has been shown to be associated with a reduction in serum testosterone level in males. This reduction in testosterone is reversible by thyroxine replacement therapy. However, to the best of our knowledge, it is not yet known, whether a similar reduction in serum testosterone level is observed in subclinically hypothyroid males [thyroid-stimulating hormone (TSH) < 10 mIU/L] in whom the benefits of thyroxine replacement therapy are still controversial. Our goal was to investigate the putative connections between subclinical hypothyroidism and the circulating levels of gonadotrophins and gonadal steroids in males (mean age +/- SEM, 34.67 +/- 1.52 years; ranging from 20 to 54 years). The serum samples from patients showing normal euthyroid and subclinical hypothyroid profiles (TSH < 10 mIU/L) were further analysed for the levels of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, progesterone and oestradiol. Subclinical hypothyroidism was associated with a decrease in the levels of serum testosterone and its precursor progesterone. The data suggest that serum testosterone declines because of the non-availability of its precursor progesterone. The level of oestradiol was similar in both the groups, suggesting a greater conversion rate of testosterone to oestradiol in subclinically hypothyroid males, in order to maintain the oestradiol levels. Prolactin levels were slightly but significantly increased in subclinical hypothyroidism. To the best of our information this is a novel report, which shows a direct association between subclinical hypothyroidism and hypoandrogenaemia. Testosterone deficiency and its symptoms should be kept in view while managing subclinical hypothyroidism in male patients. Further studies are needed in order to reveal the physiological and molecular mechanisms leading to hypoandrogenaemia in subclinical hypothyroidism (TSH < 10 mIU/L).
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PMID:Hypoandrogenaemia is associated with subclinical hypothyroidism in men. 1687 21

Leptin is an important hormone regulating nutritional status in humans and animals. Its most relevant activity is at the hypothalamic level, where it modulates food behavior, thermogenesis, and secretion of several pituitary hormones. The exact mechanisms underlying these processes are unclear. The purpose of this study was to verify whether leptin could modulate growth hormone (GH) and prolactin (PRL) secretion acting directly on bovine pituitary cells. Adenohypophyseal explants were cultured with different concentrations of leptin (50, 250, and 500 ng/mL); GH and PRL concentrations in culture media were determined by RIA. On tissues treated with 250 ng/mL of leptin, GH and PRL mRNA, as well as protein content, were estimated by reverse transcription-PCR and Western immunoblotting, respectively. Concentrations of GH in culture media containing 250 and 500 ng/mL of leptin were significantly higher than in controls: 1,063.5 +/- 141.2 (mean +/- SEM) and 1,018.8 +/- 88.4 vs. 748.9 +/- 74.0 ng/mg of tissue, respectively, after 1 h of treatment. Prolactin concentrations were significantly higher in culture media containing 50, 250, and 500 ng/mL of leptin than in controls after 2 h of treatment (547.1 +/- 50.3, 547.5 +/- 58.8, and 577.0 +/- 63.7 vs. 406.8 +/- 43.9 ng/mg of tissue, respectively). Tissues cultured with 250 ng/mL of leptin had significantly higher GH mRNA and lower GH protein content than controls (389.7 +/- 17.9 vs. 289.7 +/- 16.7; 1,601.5 +/- 90.1 vs. 2,212.7 +/- 55.6 arbitrary units, respectively) after 5 h of treatment. In contrast, no significant differences were found for PRL mRNA and protein content, possibly because of a delay in the leptin stimulation of PRL secretion. The results suggest that GH and PRL secretion in bovine pituitary explants can be directly regulated by leptin.
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PMID:Role of leptin on growth hormone and prolactin secretion by bovine pituitary explants. 1736 8


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